Progress in the development of tissue-based biomarkers for urothelial cancer

As the understanding of molecular mechanisms of bladder cancer advances, molecularly-guided precision medicine becomes increasingly relevant. Biomarkers play a critical role in this setting, predicting treatment response and identifying candidates for targeted therapies.Current literature on biomarkers in their role in disease prognosis and response to neoadjuvant and adjuvant therapies. In non-muscle invasive bladder cancer, particular focus is on markers of disease progression, and response to intravesical therapy. In muscle invasive and advanced bladder cancer, particular emphasis is on markers associated with neoadjuvant chemotherapy, as well as systemic immunotherapy. We discuss current shortcomings and pitfalls in contemporary markers, and future avenues of prospective research.The focus on biomarkers has moved from immunohistochemical analysis and tumor-related phenotypic changes to examining genetic alterations. Single marker analysis has been shown to be insufficient in predicting both disease course and response to therapy, and studies have shifted toward examining marker combinations and genetic classifiers. Ultimately, significant progress in implementing biomarkers into clinical guidelines remains elusive, largely due to lack of prospective studies in well-defined patient cohorts and with clinically meaningful endpoints. Until then, despite their promising value, tissue markers should be limited to experimental settings and clinical trials.